16-27618340-G-C

Variant names:

• chr16-27618340-G-C
• rs4787980
• NM_015202.5:c.64-85G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015202.5(KATNIP):​c.64-85G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.859 in 1,059,112 control chromosomes in the GnomAD database, including 391,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (54896 hom., cov: 31)
  • Exomes 𝑓: 0.86 (337051 hom.)
• Consequence: KATNIP NM_015202.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.159
• Publications: 5 publications found

Genes affected

KATNIP (HGNC:29068): (katanin interacting protein) This gene encodes a novel, evolutionarily conserved, ciliary protein. In human hTERT-RPE1 cells, the protein is found at the base of cilia, decorating the ciliary axoneme, and enriched at the ciliary tip. The protein binds to microtubules in vitro and regulates their stability when it is overexpressed. A null mutation in this gene has been associated with Joubert syndrome, a recessive disorder that is characterized by a distinctive mid-hindbrain and cerebellar malformation and is also often associated with wider ciliopathy symptoms. Consistently, in a serum-starvation ciliogenesis assay, human fibroblast cells derived from patients with the mutation display a reduced number of ciliated cells with abnormally long cilia. [provided by RefSeq, Feb 2016]

KATNIP Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Joubert syndrome 26

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 16-27618340-G-C is Benign according to our data. Variant chr16-27618340-G-C is described in ClinVar as Benign. ClinVar VariationId is 1250543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015202.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNIP	NM_015202.5	MANE Select	c.64-85G>C		intron	N/A	NP_056017.4	O60303

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNIP	ENST00000261588.10	TSL:1 MANE Select	c.64-85G>C		intron	N/A	ENSP00000261588.4	O60303
	KATNIP	ENST00000862512.1		c.64-85G>C		intron	N/A	ENSP00000532571.1
	KATNIP	ENST00000568258.5	TSL:3	c.49-85G>C		intron	N/A	ENSP00000454884.1	H3BNJ6

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129094 AN: 152072 Hom.: 54851 Cov.: 31

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.812

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.877

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.844

GnomAD4 exome AF: 0.861 AC: 780686 AN: 906922 Hom.: 337051 AF XY: 0.864 AC XY: 407350 AN XY: 471278

African (AFR) AF: 0.829 AC: 18900 AN: 22792

American (AMR) AF: 0.832 AC: 35154 AN: 42272

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 17431 AN: 21786

East Asian (EAS) AF: 0.999 AC: 36382 AN: 36432

South Asian (SAS) AF: 0.937 AC: 68571 AN: 73192

European-Finnish (FIN) AF: 0.879 AC: 43856 AN: 49916

Middle Eastern (MID) AF: 0.838 AC: 3895 AN: 4646

European-Non Finnish (NFE) AF: 0.848 AC: 520909 AN: 614206

Other (OTH) AF: 0.854 AC: 35588 AN: 41680

GnomAD4 genome AF: 0.849 AC: 129193 AN: 152190 Hom.: 54896 Cov.: 31 AF XY: 0.849 AC XY: 63188 AN XY: 74394

African (AFR) AF: 0.826 AC: 34297 AN: 41508

American (AMR) AF: 0.832 AC: 12712 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.812 AC: 2820 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5146 AN: 5164

South Asian (SAS) AF: 0.941 AC: 4545 AN: 4828

European-Finnish (FIN) AF: 0.877 AC: 9287 AN: 10592

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.846 AC: 57554 AN: 68018

Other (OTH) AF: 0.845 AC: 1787 AN: 2114

Alfa AF: 0.846 Hom.: 6420

Bravo AF: 0.844

Asia WGS AF: 0.968 AC: 3365 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.65
PhyloP100		0.16
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4787980; hg19: chr16-27629661;